Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation

NCT01278745 | Terminated Phase 2 Results DMC

• 1 other identifier: DAIT CTOT-11
• Study Type: interventional
• Target: 362
• Locations: 1 country
• Sites: 24

Brief Summary

All people who have a heart transplant are at risk for developing cardiac allograft vasculopathy (CAV). CAV means narrowing of the heart transplant vessels, which is associated with poor heart transplant function. People who develop antibodies after transplant have a higher risk of developing CAV. Infections, high cholesterol, and rejection also increase the risk of developing CAV. People who develop CAV usually have to receive another transplant.

Conditions

Cardiac Allograft Vasculopathy; Heart Transplant Recipients

Keywords

cardiac allograft vasculopathy (CAV); prevention; cardiac transplantation; rituximab

Outcome Measures

Primary Outcomes (1)

• Change in Percent Atheroma Volume (PAV)

  Nominal or noticeable change, bad or good, from baseline to 1 year in percent atheroma volume (PAV) which is a measure of the degree of coronary arterial obstruction due to host alloimmune processes measured by intravascular ultrasound (IVUS) in a target coronary artery. Thus a decrease in PAV would be an indicator of less obstruction and a better outcome.

  Baseline, 1 year

Secondary Outcomes (12)

• Death

  12 months

• Re-transplantation or Re-listed for Transplantation

  6 to 12 months

• Number of Episodes of Biopsy Proven Acute Rejection (BPAR) of Any Grade Per Participant

  6 to 12 months

• Incidence of BPAR (Any Grade)

  6 to 12 months

• Incidence of AMR

  6 to 12 months

Study Arms (2)

Rituximab

EXPERIMENTAL

Rituximab induction/conventional immunosuppression

Biological: Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)

Rituximab Placebo

PLACEBO COMPARATOR

Rituximab Placebo / conventional immunosuppression

Drug: Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)

Interventions

Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper) BIOLOGICAL

Rituximab

Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper) DRUG

Rituximab Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be able to understand and provide informed consent;
• Male or Female, 18 to 75 years of age;
• Candidate for a primary heart transplant (e.g., listed for heart transplant only);
• Historical panel reactive antibodies (PRA) less than 30%;
• Calculated GFR ≥ 40 mL/minute using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI);
• Female and male subjects with reproductive potential, must agree to use FDA approved methods of birth control for the duration of the study
• Negative PRA within 12 weeks prior to transplant (Local HLA Center Testing) using one of the following:
• One Lambda's LABScreen® Mixed Class I \& II (presence or absence), or
• Less than 10% by One Lambda's LABScreen® PRA Class I and II with an MFI of \<2000, or
• Calculated panel reactive antibodies (cPRA) less than 10% by LABScreen® Single Antigen testing (Anti-HLA-A, -B, -DR, -DQ). The antigens reported will include those with an MFI \>2000.
• The Luminex Gen-Probe beads are equivalent to the One Lambda and may be used as an alternative;
• Calculated GFR ≥ 40mL/minute using the CKD-EPI at time of randomization;
• Serum immunoglobulin G (IgG) level greater than 500mg/dL within 90 days prior to randomization;
• Negative test for HIV, HBsAg, HBcAb, and HCV Ab within 12 months prior to transplant. If documentation is not present to support that the testing was performed in the past 12 months, then a blood sample will be collected prior to transplant and sent for local testing. Results may be available after randomization. If positive result, the oversight committee will review the case and provide further recommendations.
• Female subjects of childbearing potential must have a negative pregnancy test.

You may not qualify if:

• Prior history of organ transplantation;
• Previous treatment with Rituximab (MabThera® / Rituxan ®);
• Transplant physician intention to use any induction agents;
• History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies;
• History of severe reaction to previous therapy with IVIG;
• Active systemic infection at time of enrollment;
• Any history of serologic positivity to HIV, HBsAg, HBcAb, and HCV Ab;
• History of less than 5 years remission of malignancy. Any history of adequately treated in-situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of the skin will be permitted;
• Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
• Use of other investigational drugs within 4 weeks of enrollment;
• Currently breast-feeding or plans to become pregnant during the timeframe of the study follow-up period.
• Recipient of multiple solid organ or tissue transplants;
• Previous treatment with Rituximab (MabThera® / Rituxan ®);
• Use of any induction agents;
• History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Clinical Trials in Organ Transplantation: collaborator
• Genentech, Inc.: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (24)

Cedars Sinai Heart Institute

Beverly Hills, California, 90211, United States

Location

Ronald Regan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Stanford University/Palo Alto VA

Palo Alto, California, 94304, United States

Location

University of California San Francisco

San Francisco, California, 94143-0124, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032', United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Medical City Dallas Hospital/CRSTI

Dallas, Texas, 75230, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

University of Utah

Salt Lake City, Utah, 84132-2401, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Starling RC, Armstrong B, Bridges ND, Eisen H, Givertz MM, Kfoury AG, Kobashigawa J, Ikle D, Morrison Y, Pinney S, Stehlik J, Tripathi S, Sayegh MH, Chandraker A; CTOT-11 Study Investigators. Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation. J Am Coll Cardiol. 2019 Jul 9;74(1):36-51. doi: 10.1016/j.jacc.2019.04.056.

  PMID: 31272550 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Clinical Trials in Organ Transplantation (CTOT) website
• National Heart, Lung, and Blood Institute (NHLBI) website

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

The study was terminated with 163 participants randomized, well short of the study's goal of 300 randomized participants.

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Randall Starling, MD

  The Cleveland Clinic

  STUDY CHAIR

• Mohamed Sayegh, MD

  Brigham and Women's Hospital/Harvard

  PRINCIPAL INVESTIGATOR

• Anil Chandraker, MD

  Brigham and Women's Hospital/Harvard

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2011
• First Posted: January 19, 2011
• Study Start: September 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: August 25, 2020
• Results First Posted: April 11, 2017

Record last verified: 2020-08

Locations

US (24)